title: Increased apparent diffusion coefficients on MRI linked with matrix metalloproteinases and edema in white matter after bilateral carotid artery occlusion in rats.
abstract: White matter (WM) injury after bilateral common carotid artery occlusion (BCAO) in rat is associated with disruption of the blood-brain barrier (BBB) by matrix metalloproteinases (MMPs). We hypothesized that WM injury as seen on magnetic resonance imaging (MRI) would correlate with regions of increased MMP activity. MRI was performed 3 days after BCAO surgery in rats. Apparent diffusion coefficients (ADC) were calculated and vascular permeability was quantified by the multiple-time graphical analysis (MTGA) method, using gadolinium-diethylenetriamine pentaacid (Gd-DTPA). After MRI, one group of animals had BBB permeability measured in the WM with (14)C-sucrose, and another had Evans blue (EB) injected for fluorescent microscopy for MMP-2, MMP-9, tight junction proteins (TJPs), and in situ zymography. We found that ADC values were increased in WM in BCAO rats compared with controls (P<0.05). WM with increased ADC had leakage of EB. MMP-2 and MMP-9 activity on in situ zymograms corresponded with leakage of EB. Although increased permeability to EB could be visualized, permeability quantification with (14)C-sucrose and Gd-DTPA failed to show increases and TJPs were intact. We propose that increased ADC, which is a marker of vasogenic edema, is related to activity of MMP-2 and MMP-9. MRI provides unique information that can be used to guide tissue studies of WM injury.
authors.affiliation: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. rsood@salud.unm.edu
authors.forename: Rohit
authors.initials: R
authors.lastname: Sood
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Saeid
authors.initials: S
authors.lastname: Taheri
authors.forename: Eduardo
authors.initials: E
authors.lastname: Candelario-Jalil
authors.forename: Eduardo Y
authors.initials: EY
authors.lastname: Estrada
authors.forename: Espen J
authors.initials: EJ
authors.lastname: Walker
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thompson
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology*; D062507:Claudin-5; D004058:Diffusion; D004487:Edema / Q000201:enzymology* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D020782:Matrix Metalloproteinases